Benzo[a]pyrene (BP) is a ubiquitous carcinogen found in tobacco smoke, burning or fossil fuels, and our diet. Formation of BP diol epoxide (BPDE)-DNA adducts due to human exposure is most likely to be at very low levels that are beyond the sensitivity of routine radioimmunoassay and chromatographic analysis. Thus, ultrasensitive enzymatic radioimmunoassay (USERIA), enzyme-linked immunosorbent assay (ELISA), and photon counting synchronous scanning fluorimetry have been employed to detect and quantitate BPDE-DNA adducts in humans at high cancer risk due in part to BP exposure. DNA isolated from white blood cells of asphalt workers (roofers) and foundry workers and DNA from lung tissue, bronchial washings, and alveolar macrophages of lung cancer patients and smokers are being investigated. BP-DNA adducts have been detected in several of the high-risk individuals. Antibodies to BPDE-DNA adducts were also found in sera from those workers. These data suggest that the activation of BP to its ultimate carcinogen as well as formation of adducts with DNA occurs in humans.